A comparative study of the relationship between histocompatibility and pregnancy in the genus Equus is proposed. Preliminary studies using conventional alloantisera, mixed lymphocyte cultures, and xenogeneic monoclonal antibodies have defined a polymorphic, polyallelic genetic system of lymphocyte alloantigens in the horse (the Equine Leukocyte, or ELA Antigens) which is probably the Major Histocompatibility Complex (MHC) of the equine. The horse has been chosen as a model for these studies for two principal reasons: 1) Mares in their first pregnancy make strong cytotoxic alloantibody responses to ELA antigens by day 60 in a 330 day gestation; 2) We have preliminary evidence for a decreased frequency of homozygous offspring in breeding populations and an excess of females among homozygotes. If there are important biological phenomena linking mammalian reproduction and histocompatibility, they should be discernible in the horse, where the evidence for strong, early maternal immunological recognition of the fetus is overwhelming. In this study, using various immunohistochemical techniques and conventional alloantisera and monoclonal antibodies directed against equine tissue alloantigens, we will attempt to identify and characterize the source of paternal histocompatability antigens derived from the fetal-placental unit which are exposed to the maternal immune system. We will determine the relationship between histoincompatibility and gonadotropin secretion and investigate the role of ELA incompatibility in spontaneous early abortion. We will compare the maternal immune response to tissue alloantigens in closely related species of equids and attempt to correlate differences with physiological or anatomical differences between the species. We will conduct a large scale genetic investigation to confirm our preliminary results concerning the distortion of sex ratios in homozygous offspring. We will determine if particular ELA antigens are disfavored in the homozygous state. We will investigate the possibility that the distorted segregation and sex ratios reflect a maternal immune response to the H-Y antigen. These results will contribute to our continuing investigations of the biological significance of the MHC in natural populations and the role of tissue incompatibility in mammalian pregnancy.